Vitamin K Supplementation in Post-Menopausal Osteopenia

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00150969
First received: September 6, 2005
Last updated: November 19, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.


Condition Intervention Phase
Post-Menopausal Osteoporosis
Post-Menopausal Osteopenia
Dietary Supplement: vitamin K1 (phylloquinone)
Dietary Supplement: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia (ECKO Trial)

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer


Secondary Outcome Measures:
  • Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    measured by osteocalcin on elecsys platform

  • Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX) [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    measured by CTX Elisa assay on elecsys platform

  • Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin [ Time Frame: 0 to 24 months ] [ Designated as safety issue: No ]
    measured by osteocalcin hydroxyapatite binding assay

  • Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms. [ Time Frame: 0 to 48 months ] [ Designated as safety issue: No ]
    BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

  • Difference in Serious Adverse Events [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
    These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.

  • Difference in Number of New Cancers by Treatment Arm. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
  • Difference in Number of New Clinical Fractures by Treatment Arm. [ Time Frame: up to 48 months ] [ Designated as safety issue: Yes ]
    these included fragility fractures


Enrollment: 440
Study Start Date: January 2002
Study Completion Date: September 2007
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: phyloquinone
5 mg Vitamin K1
Dietary Supplement: vitamin K1 (phylloquinone)
Placebo Comparator: placebo Dietary Supplement: placebo
1 pill daily

Detailed Description:

Osteoporosis is major cause of morbidity and mortality in Canadian postmenopausal women. It is a systemic disease characterized by low bone mass and deterioration of bone microarchitecture, resulting in bone fragility and an increased risk of fractures. One in six women over the age of 50 have osteoporosis. The lifetime risk of an osteoporotic fracture for an average 50 year-old Canadian woman is >40%. The annual health care costs for osteoporotic fractures in Canada have been estimated to exceed $1.3 billion.

Recent data suggest that vitamin K supplements may decrease bone loss and prevent fractures. Vitamin K is a co-factor of gamma-glutamyl carboxylase, an enzyme that catalyzes the gamma-carboxylation of glutamic acid residues in bone matrix proteins such as osteocalcin. Vitamin K has been reported to enhance bone formation in both in vitro studies and in vivo studies in animals. Vitamin K levels are low in individuals with osteoporosis and in patients with osteoporotic fractures. The few studies examining vitamin K supplementation in humans have showed promising results with no significant side effects, but these studies had significant methodological shortcomings such as inadequate sample size and lack of randomization.

The primary objective of our study is to examine whether vitamin K supplementation will increase bone mineral density in postmenopausal women with osteopenia. Our secondary objectives are to examine the possible adverse effects from long-term vitamin K supplementation, to investigate whether vitamin K will decrease risk of fractures and to determine if vitamin K affects quality of life. Our hypotheses are that vitamin K increases bone mineral density in postmenopausal women, and that there are no significant adverse effects from vitamin K supplementation.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Postmenopausal: One year since the natural cessation of menses, or Hysterectomy with either postmenopausal status confirmed by FSH lab values, or age 55 and above AND 2. Osteopenic: T-score at baseline has to be between (and including) -1.0 and

-2.0 in the lumbar spine (L1-L4), total hip or femoral neck, and the lowest reading of the above three measurements must be between -1.0 and -2.0

Exclusion Criteria:

  1. Women ever having had a fragility fracture after age 40;
  2. Women currently on anticoagulants, previously on anticoagulants in the past 3 months, or expected to be on anticoagulants in the near future;
  3. Women on hormone replacement therapy, raloxifene, bisphosphonates or calcitonin during the past 3 months;
  4. Women who have ever been on a bisphosphonate for more than 6 months;
  5. Women previously diagnosed with Paget's disease, hyperparathyroidism, hyperthyroidism or other metabolic bone diseases;
  6. Women with decompensated diseases of the liver, kidney, pancreas, lung, or heart;
  7. Women with a history of active cancer in the past 5 years;
  8. Women taking mega-doses of vitamin A (more than 10,000 iu per day) or E (more than 400 iu per day);
  9. Women involved in other clinical trials;
  10. Any women who, in the opinion of the principal investigator, is at poor medical or psychiatric risk for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150969

Locations
Canada, Ontario
University Health Network, Osteoporosis Department
Toronto, Ontario, Canada, M5G 2C4
St. Michael's Hospital Health Centre
Toronto, Ontario, Canada, M5C 2T2
Sunnybrook & Women's College Health Sciences Centre
Toronto, Ontario, Canada, M5S 1B2
Mt. Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
University of Toronto
Toronto, Ontario, Canada, M5S 3E2
Sponsors and Collaborators
University Health Network, Toronto
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Angela M Cheung, MD, PhD University Health Network, University of Toronto
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00150969     History of Changes
Other Study ID Numbers: CIHR-50422
Study First Received: September 6, 2005
Results First Received: January 10, 2012
Last Updated: November 19, 2012
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
vitamin K
bone mineral density
post-menopausal women
randomized double blind placebo controlled trial
osteoporosis
women's health

Additional relevant MeSH terms:
Bone Diseases, Metabolic
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases
Musculoskeletal Diseases
Vitamin K 1
Vitamin K
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014